Perturbed activity-dependent plasticity mechanisms in autism

The researchers plan to study synapse formation in neurons deficient for autism-associated genes, including members of the Shank, neurexin, and neuregulin families, specifically looking for defects in the activity-dependent final steps. Using a combination of optics and chemistry, the researchers plan to carefully control the release of the neurotransmitter glutamate sensed by a dendritic spine. This technique will mimic the release of glutamate from the axon and trigger the electrochemical pulses that would normally be induced in the spine. The researchers then plan to look for changes in the number of synapses and in the morphology and composition of the dendritic spines. Based on their hypothesis that autism-related proteins assist in synapse formation, the researchers expect that loss of the proteins will cause consistent defects in these structures and in their signaling strength, which may underlie the learning and social impairments seen in people with autism.